Bristol-Myers Squibb (BMY) Receives EC Approval for Opdivo in Combination with Cabometyx as First-Line Treatment for Patients with Advanced Renal Cell Carcinoma

Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo® (nivolumab) in combination with Cabometyx® (cabozantinib) for the first-line treatment of adults with advanced renal cell carcinoma (RCC). The EC’s decision is based on results from the Phase 3 CheckMate -9ER trial, which demonstrated superior efficacy with Opdivo in combination with Cabometyx versus sunitinib across three key endpoints: progression-free survival (PFS), the primary endpoint, and objective response rate (ORR) and overall survival (OS). The combination of Opdivo and Cabometyx was well tolerated, with safety reflective of the known profiles of both medicines and a low rate of treatment-related adverse events (TRAEs) leading to discontinuation.

“With this approval, we can now offer patients two different Opdivo-based combinations that have demonstrated significant survival benefits versus sunitinib,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. “Today’s milestone builds on our heritage of developing and delivering novel treatments for patients with advanced renal cell carcinoma, first with the only dual immunotherapy option, Opdivo plus Yervoy, and now with a new immunotherapy and tyrosine kinase inhibitor regimen. We look forward to working with a broad range of European stakeholders to bring Opdivo in combination with Cabometyx to patients who may benefit from this treatment.”

“The combination of nivolumab and cabozantinib pairs two proven agents for advanced renal cell carcinoma that together have shown superior efficacy across key endpoints and subgroups of patients compared to sunitinib in the CheckMate -9ER trial. Additionally, the combination’s safety profile was manageable with known protocols, leading to a low rate of treatment-related discontinuations,” said Marc-Oliver Grimm, M.D., professor of medicine and urology department head, Jena University Hospital. “With today’s approval, clinicians in the EU will be able to offer patients with advanced renal cell carcinoma an additional combination therapy that may help them achieve early control of their disease and improve survival outcomes.”

Opdivo in combination with Cabometyx was approved for RCC in the EU with a flexible dosing regimen, with the option to use either Opdivo 240 mg administered intravenously every two weeks or Opdivo 480 mg administered intravenously every four weeks in combination with Cabometyx 40 mg administered orally once daily.

In addition to the EU, Opdivo in combination with Cabometyx was approved for the first-line treatment of advanced RCC by the U.S. Food and Drug Administration in January 2021, and further applications are under review with health authorities globally. Results from the CheckMate -9ER trial were published in the New England Journal of Medicine in March 2021.

“With progress in research, patients are living longer with advanced kidney cancer than ever before, and so it has become increasingly important to consider how treatment impacts their daily lives,” said Rachel Giles, M.D., Ph.D., chair, International Kidney Cancer Coalition. “We are pleased to see the approval of a new, first-line combination for patients with advanced renal cell carcinoma that has the potential to not only control the disease but also maintain their health-related quality of life.”

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

CheckMate -9ER Efficacy and Safety Results

In the CheckMate -9ER trial, Opdivo in combination with Cabometyx showed superior PFS, ORR and OS versus sunitinib, with a low rate of TRAEs leading to discontinuation. With a minimum follow-up of 10.6 months:

• PFS: Opdivo in combination with Cabometyx doubled median PFS (16.6 months vs. 8.3 months, respectively; HR 0.51; 95% CI: 0.41 to 0.64; p <0.0001), the trial’s primary endpoint, compared to sunitinib.
• OS: The combination reduced the risk of death by 40% compared to sunitinib (HR: 0.60; 98.89% CI: 0.40 to 0.89; p=0.0010; median OS non-estimable for either arm).
• ORR: Twice as many patients responded to Opdivo in combination with Cabometyx compared to sunitinib (55.7% vs. 27.1%).
• Grade 3+ adverse events: Adverse reactions Grade 3 or higher in the trial were similar with Opdivo in combination with Cabometyx versus sunitinib (75% versus 71%).
• TRAE discontinuations: Among patients treated with Opdivo and Cabometyx, 5.6% discontinued both agents due to TRAEs, 6.6% discontinued Opdivo only and 7.5% discontinued Cabometyx only. In the sunitinib arm, 8.8% of patients discontinued due to TRAEs.

An updated analysis conducted with 16.0 months minimum follow-up showed sustained efficacy improvements with Opdivo in combination with Cabometyx compared to sunitinib. These data were presented at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium.

With a minimum follow up of 16.0 months, the most frequent adverse reactions, occurring in 10% or more of patients, were diarrhea (64.7%), fatigue (51.3%), palmar-plantar erythrodysaesthesia syndrome (40.0%), stomatitis (38.8%), musculoskeletal pain (37.5%), hypertension (37.2%), rash (36.3%), hypothyroidism (35.6%), decreased appetite (30.3%), nausea (28.8%), abdominal pain (25.0%), dysgeusia (23.8%), upper respiratory tract infection (20.6%), cough (20.6%), pruritus (20.6%), arthralgia (19.4%), vomiting (18.4%), dysphonia (17.8%), headache (16.3%), dyspepsia (15.9%), dizziness (14.1%), constipation (14.1%), pyrexia (14.1%), edema (13.4%), muscle spasm (12.2%), dyspnea (11.6%), proteinuria (10.9%) and hyperthyroidism (10.0%).

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